20-hydrocarbyl-6-keto-steroids

ABSTRACT

This invention is directed to 2,3-substituted-20-hydrocarbyl 6keto-steroids which are useful as metamorphosis hormones and are additionally useful as intermediates for the production of other insect hormones. Accordingly, the compounds may be employed in the control of insect population.

United States Patent [191 v Furst et al.

[ 5 4 20-HYDROCARBYL-6-KETO-STEROIDS [73] Assignee: Hoffmann-La Roche Inc., Nutley,

[22] Filed: Feb. 29, 1968 [21] Appl. No.: 709,239

Related US. Application Data [62] Division of Ser. No. 571,187, Aug. 9, 1966.

260/3974, 260f397.45, 260/3971, 195/51 [51 Int. Cl. ..C07c 173/00 [58] Field ofSearch 260/239.55 D, 397.2, 397.4

11] 3,835,127 Sept. 10, 1974 [56] References Cited UNITED STATES PATENTS 3,354,154 6/1967 Edwards et al. 260/239.55 3,378,549 4/1968 Edwards et al. 260/239.55 3,655,650 4/1972 Furst et al 260/239.55

Primary ExaminerElbert L. Roberts Attorney, Agent, or Firm-Samuel L. Welt; Jon S. Saxe; William H. Epstein [57] ABSTRACT This invention is directed to 2,3-substituted-20- hydrocarbyl 6-keto-steroids which are useful as metamorphosis hormones and are additionally useful as intermediates for the production of other insect hormones. Accordingly, the compounds may be employed in the control of insect riopulation.

21 Claims, No Drawings 20-HYDROCARBYL-6-KETO-STEROIDS RELATED APPLICATIONS This application is a division of applicants copending 5 application Ser. No. 571,187, filed Aug. 9, 1966. Other related applications of Ser. No. 571,187 filed by the applicants, include PROCESS FOR THE PREPARA- TION OF 58B-I-l-6-KETO-STEROIDS, Ser. No.

709,238, filed Feb. 29, 1968, now US. Pat. No.

3,557,097 22-FUNCTIONALlZED-6-KETO- STEROIDS, Ser. No. 709,187, filed Feb. 29, 1968, now US. Pat. No. 3,547,910 and 5B-H-6-KETO- PREGNANE-DERIVATIVES, Ser. No. 709,186, filed Feb. 29, 1968, now US. Pat. No. 3,651,100.

DETAILED DESCRIPTION OF THE INVENTION Ra a|.....

R l Rn a [1A RbNw L o .(l)

wherein R is hydrogen or methyl; R" is hydrogen, hydroxy, lower acyloxy, or lower alkoxy; R is hydroxy, lower acyloxy, or lower alkoxy; or lower alkoxy; R and R", when taken together and when R is in the B-orientation, are lower alkylenedioxy; A represents a single or a double bond; R is hydrogen or hydroxy; R is hydrogen or lower alkyl; R, when R is lower alkyl, is hydroxy or lower acyloxy, and when R is hydrogen, is hydroxy, lower acyloxy, or a radical of the formula C(CI-I )RR; R, when taken alone, is hydrogenor hydroxy; R, when taken alone, is CO Z, CI-IO, CH(O-lower alkyl) (CH CO Z, aliphatic hydrocarbyl or aliphatic hydrocarbyl substituted with up to two substituents of the group consisting of hydroxy, lower acyloxy, lower alkoxy, or tetrahydropyranyloxy; R and R, when taken together, are

0x0; and Z is hydrogen or lower alkyl.

By the term lower acyloxy is meant a radical derived from an aliphatic carboxylic acid of up to about 1 1 carbons by removal of the hydrogen of the carboxyl group. The acid may be saturated or unsaturated, straight or branched chain, and may contain one or more substituents, such as halo, including chloro and fluoro, nitro, oxy, and the like. Suitable acids include formic acid, acetic acid, propionic acid, trimethylacetic acid, caproic acid, enanthic acid, hendecanoic acid, phenylacetic acid, benzoic acid, cyclopentylpro- 65 pionic acid, trifluoroacetic acid, aminoacetic acid, oxypropionic acid, adipic acid, and the like. Preferred are hydrocarbyl acyclic mono-basic acids of up to about 6 carbons, with alkanoic mono-carboxylic acids being especially preferred.

By the terms lower alkyl and lower alkoxy are meant alkyl and alkoxy groups of up to about six carbons, such as methyl, ethyl, propyl, isopropyl, butyl, tert.-butyl, hexyl, methoxy, ethoxy, tert.-butoxy, and the like.

By the term lower alkylenedioxy group is meant a divalent radical of the formula -ORO, wherein R' is an alkylene, i.e., a divalent saturated acyclic hydrocarbon, radical of up to about 10 carbons, and preferably up to about six carbons. Especially preferred are alkylidenedioxy groups, with isopropylidenedioxy being most preferred.

By the term aliphatic hydrocarbyl group is meant a mono-valent radical free of aromatic unsaturation and consisting of carbon and hydrogen, such as alkyl, alkenyl, alkynyl, alkadienyl, and the like, and may be either branched or straight chain. Preferred aliphatic hydrocarbyl groups are alkyl groups and alkynyl groups of up to about six carbons, such as ethynyl, propyl, isopropyl, butyl, isobutyl, butynyl, pentyl, isopentynyl, and the like, with branched-chain groups being preferred. Preferred substituted aliphatic hydrocarbyl groups are those represented by the formula -CI-I- (OH)R", wherein R" is aliphatic hydrocarbyl of up to about five carbons, preferably branched chain, and especially branched alkyl or alkynyl, which may be substituted with a hydroxyl group, a lower alkyl group, a lower alkoxy group, or a tetrahydropyranyl 'group.

The novel products of this invention are illustrated by the following formulae:

0 v (II) wherein R and R are as defined above;

R and r each taken alone, is hydroxy, lower acyloxy, or lower alkoxy, and R R can be the same or different;

R and R when taken together, and R is in the B-orientation, are lower alkylenedioxy;

A is as defined above;

R is hydrogen or lower alkyl;

R, when R is lower alkyl, is hydroxy or lower acyloxy, and when R is hydrogen, is hydrogen;

lower acyloxy, or a radical of the formula -C(CH )R R R when taken alone, is hydrogen or hydroxy;

R when taken alone, is CO Z, CHO,

CH-(O-lower alkyl) (CH -CO aliphatic hydrocarbyl, or aliphatic hydrocarbyl substituted with up to two substituents of the group consisting of hydroxy, lower acyloxy, lower alkoxy, or

tetrahydropyranyloxy; R when taken alone, and when R is hydrogen, is CO Z, -CHO, CH(O-lower alkyl) invention are those defined by the formula:

on COzZ 0 CH3 l wherein R R R, A, and Z are as defined above.

It is also within the contemplation of the present invention that the steroids of Formulae l-Vl may have sustituents or unsaturated carbon-carbon bonds other than those specifically depicted. For example, a lower alkyl group may be present on the l- 7-, or 16- present in the l-, 11-, 16, or 17-positions, and double bonds may be present in the l(2)- and/or the 3(4)- positions.

The production of SB-H-steroids of the type defined by Formulae II, III, and VI is unexpected in view of the teachings of A. Schubert, J. Org. Chem, 26 159 (1964); H. B. Henbest, J. Chem. Soc., 1957, 4596 and 4765; and N. L. Allenger, J. Org. Chem, 26, 3626 (1961). These publications disclose that 5BH6- ketosteroids which are unsubstituted in the 2-position are isomerized under acidic or basic conditions to the corresponding Sa-H-steroids, thus, thus leading to the conclusion that the A/B-trans-ring linkage is the more stable form for 6-ketosteroids. Unexpectedly, it has been discovered by this invention that 6-ketosteroids substituted in both the 2- and 3-positi0ns hydroxy groups or esterified or etherified hydroxy groups and having an A/B-cis-ring linkage are stable.

The various products of this invention are obtained by both known and novel reactions from known starting materials such as A -cholesten-6-one, methyl 3,3- ethylenedioxy-A -pregnen-20-carboxylate, 3-hydroxy- A -cholesten-6-one, 3-acetoxy-A"' ergostadien-6-one,

Equation A: .4

CH3 B :113

wherein B represents the remainder of the steroid nucleus. This process is particularly useful for producing a compound of Formula II above from the corresponding Sa-H-steroid.

The isomerization is effected by the introduction of energy such as by thermal energy, irradiation, and the like, preferably in the presence of an inert organic solventfSuitable solvents include alcohols such as methanol and ethanol; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, and dioxane; ketones such as acetone and methyl ethyl ketone; esters such as ethyl acetate; hydrocarbons such as benzene; chlorinated hydrocarbons such as chloroform; and the like.

The introduction of thermal energy is effected by heating at elevated temperatures, such as at about 50C. or higher, and preferably in the range of from about 60 to about C. The presence of acidic or basic catalysts, heretofore known as isomerization catalysts, promotes the rate of isomerization and permits the use of lower temperatures. Suitable acid catalysts include sulfuric acid, penchloric acid, selenous acid, p-toluene-sulfonic acid, and Lewis acids such as boron trifluoride, magnesium bromide, mercury chloride, aluminum chloride, and the like. Basic catalysts which can be employed include inorganic bases such as alkali metal hydroxides, for example, sodium hydroxide or potassium hydroxide, and alkaline earth metal hydroxides, for example, calcium hydroxide or magnesium hydroxide; as well as basic salts such as potassium carbonate, and the like; and organic bases such as triethylamine, benzyltrimethylammonium hydroxide, pyridine, or lutidine. In addition, acidicor or basic adsorption agents such as aluminum oxide or silica gel will also catalyze the isomertization.

The acidic or basic reaction medium, in addition to catalyzing the isomerization at the 5-position, can also be employed to promote other structural changes in the steroid. For example, selenium dioxide (selenous acid), which is employed to introduce a hydroxy group in the Mot-position, as hereinafter described, is sufficiently acidic to effect isomerization of the Sea-hydrogen to the SB-hydrogen.

The temperature and reaction time necessary to achieve the isomerization will vary depending upon the catalyst, but suitable temperatures and times can be readily determined by those having ordinary skill in the art. For example, at 60-80C. times of about 4 hours are normally employed when hydrochloric acid is employed as the catalyst, whereas about 1 hour is suffi-' cient when potassium hydroxide is employed. On the other hand, isomerization occurs at C. in less than 1 hour when boron trifluoride is the catalyst.

The isomerization of this invention may also be effected by the use of ultraviolet radiation, by which term is meant light having a wave length of less than about 4,000 Angstrom units.

The product of the isomerization, if conducted for a sufficient length of time, in an equilibrium mixture of the Sa-H- and SB-l-l-isomers in approximately equimolar amounts. At short times and/or with weak catalysts, less than an equimolar ratio of SB-H- to a-l-l-steroid is produced. These isomers may be separated, however, by techniques known to the art such as chromatography, fractional crystallization, and the like. In addition, when the isomerization product is a 2,8,3B-dihydroxy compound, the isomers may be separated by reaction with acetic anhydride. The SB-H-isomer readily forms a 2B,3B-acetate, whereas the Sa-H-isomer forms a 2B- hydroxy-BB-acetate. The diacetate is normally less so]- uble than the mono-acetate and thus can be readily precipitated from the reaction mixture. The Sa-H- monoacetate, which remains in solution, can then be subjected to a second isomerization in accordance with this invention. M

The products of this process can be hydrolyzed or acylated, if desired, by known reaction techniques. Furthermore, compounds wherein R and R when taken together are alkylenedioxy, are readily formed by the acid-catalyzed reaction of a 2,8,3B-dihydroxy compound with a ketone, for example, acetone.

A second novel reaction of this invention, and one which is related to the above-described isomerization, comprises the conversion of a 2,8,3-dihydroxy-5a-H-6- keto-N-steroid which is unsubstituted in the 14- position or a monoor diether or monoor diester thereof to the corresponding 5,8-l-l- 1 4ahydroxysteroid, as is illustrated by Equation B:

Equation B:

OH: R CH;

5 H CH3 CH3 a CH3 CH3 R1 R1 k/V K The oxirane ring of the starting material of this process may be in either the aor B-orientation. Suitable acid catalysts are those discussed above with reference to the Sa-H- to SB-H-isomerization. This reaction is normally effected in the presence of an inert organic solvent such as those discussed above. The reaction temperature is not narrowly critical, although it is preferred to employ relatively low temperatures, especially those in the range of from about 1 0C. to about +30C.

Still another novel transformation useful in producing a 2B,3,8-dihydroxy-5B-H-6-ketosteroid is that proceeding from a 3,6-dioxo-5a-H-steroid by a series of reaction illustrated by Equations D, E, and F, employing partial formulas:

Equation D:

OH; on, L l o o Equation E:

CH3 b CH3 l it 1 .on r aY 9K Equation F CH3 ona 0.. The reaction steps outlined above are novel and yield unexpected results both individually and in combination. This sequence is especially valuable for producing compounds of Formula [I wherein A represents a single bond.

In the first step of this reaction sequence (Equation D), a 3,6-dioxo-a-H-steroid is brominated by generally known techniques to produce a 2a-bromo-3,6-dioxo-5a-H- This result is unexpected in view of the disclosure of H. Sarett, J. Org. Chem. 8, 405 (1943) that the bromination of 3,6-chloranedione, a SB-H-steroid, yields a mixture of a polybromo compounds.

The bromination of this invention is effected by reacting the 3,6-diketosteroid with bormine in any suitable manner. A preferred procedure comprises dissolving the 3,6-ketosteroid in a solvent which is inert towards bormine, such as tetrahydrofuran, dioxane, ether, benzene, or chloroform, and subsequently adding to this solution a solution of bormine in acetic acid dropwise at reduced temperature, i.e., below about room temperature (25C.). On completion of the bromination, free hydrogen bromide produced by the reaction is neutralized, as by the addition of a buffer such as potassium acetate.

In the second step of this novel reaction sequence (Equation E), the 3-keto group of the 2a-bromo-3,6- diketosteroid is selectively reduced by reaction of the steroid with alithium tri(lower alkoxy) aluminum hydride, preferably a lithium tri(tert-lower alkoxy) aluminium hydride, such as lithium tri(tert.-butoxy)- aluminum hydride or lithium tri(tert.- amyloxy)aluminum hydride. This reduction is effected in an inert organic solvent such as dioxane, tetrahydrofuran, or ether, and is preferably effected at reduced temperatures, especially in the range of from about 5to about +l5C. The production of a 3B-hydroxy-6- ketosteroid in this manner is entirely unexpected, for it could not be foreseen that the 3,6-diketo system would be susceptible to selective reduction. Furthermore, if one were to predict which of the two keto groups would be more likely to be reduced, the free-standing 6-keto group would appear to be the most susceptible to preferential reduction. This is because attack at the 3-keto group by the bulky lithium tri(lower alkoxy)aluminum hydride compounds would be expected to be sterically hindered by the 2abromo atom.

The final reaction step of this sequence (Equation F) comprises the replacement of the Za-bromo atom with a ZB-acyloxy group, employing generally known techniques but leading to the unexpected SB-H-steroids. In a preferred technique, the 2a-bromo-3B- hydroxysteroid produced by the above-described selective. reduction is esterified to form a 2oz-bromo-3B- acyloxysteroid, which is then reacted with an alkali metal acylate or a silver acylate, preferably an acetate, and most desirably silver acetate. This reacion is normally effected at elevated temperatures, preferably-in the range of from about C. to about C. As with the previously described 5aH- to SB-H-isomerization, the product of this reaction is a mixture of 5aand 5B- l-l-isomers, which may be reaily separated by known techniques.

A further novel reaction sequence of this invention comprises the conversion of a 2B,3B-dihydroxy-6-keto- N-pregnen-ZO-carboxylic acid to the corresponding aldehyde,-as is illustrated by Equation G:

Equation G:

CH3 COzH CH3 CH0 CH3 CH3 CH: CHal i l R R I l m .J l

This conversion is effected by first reacting the acid, the hydroxy groups of which are preferably protected, as by conversion to acyloxy, alkoxy, or alkylenedioxy groups, with carbonyl diimidazole in accordance with known procedures to form an imidazolide. This product is then reacted with a lithium tri-(lower alkoxy)aluminum hydride to offset selective conversion of the imidazolide group to the formyl group. This reaction is unexpected because the normally used reducing agent, lithium aluminum hydride, is known to effect reduction of keto groups and elimination of ester groups. The reaction is preferably conducted in the absence of free oxygen, as in an argon or nitrogen atmosphere. The reaction temperature is not narrowly critical, although temperatures of about room temperature (20-25C.) are normally employed. The reaction is generally effected in the presence of an inert organic solvent such as those previously discussed above.

A final novel process of the present invention comprises the conversion of a 20-formylpregnan-6-one to a 20 l-hydroxy-hydrocarbyl)-pregnan-6-one, as is illustrated by Equation H:

This reaction is effected by reacting the 20-formyl compound with a Grinard reagent having the formula: R Mgx wherein R" is as defined above and X is chlorine, bromine, oriodine. This conversion is effected in the presence of an inert solvent such as those previously disclosed and preferably an ether such as tetrahydrofuran, ether, dioxane, or the like. The temperature of the re-' action is not narrowly critical, but reduced temperatures, preferably in the range of from about C. to about +C. and more especially about O5C., are employed to ensure as quantitative and selective a reaction as possible. In a preferred technique, a solution of the Grignard reagent is slowly added with stirring to a solution of the -formyl compound. The selective reaction with the 20-formyl group without attack on the 6-keto group or an acyl group is unexpected, for it is well known that Grignard reagents readily react with such groups. The reaction time is not narrowly critical, and the reaction is generally complete after about 5 to 10 minutes under the foregoing conditions. However, the reaction period can be permitted to extend as long as about 30 or even about 60 minutes without the occurrence of significant side reactions.

When R is an unsaturated group, the unsaturated side chain may be selectively hydrogenated over a metal catalyst, such as palladium, and preferably platinum dioxide, employed as such or deposited on conventional supports. The hydrogenation is preferably effected in a solvent for the steroid such as a lower alcohol, for example, methanol or ethanol; an ether, for example, diethyl ether, dioxane, or tetrahydrofuran; an ester, for example ethyl acetate; or a hydrocarbon, for example, benzene. Carboxylic acids, such as acetic acid, not desirable because they promote the reduction of the 6-keto group as well as the A-bond, if present.

When a l4a-hydroxy compound is desired as the product, the hydrogenation should be effected prior to the introduction of the l4a-hydroxy group because of the tendency of the hydrogenation to effect at least partial elimination of this group. Alternatively, the Grignard reaction may be effected with a reagent wherein R is already saturated.

The l4a-hydroxylation may be effected by known techniques, as well as by the previously described reaction with selenous acid, which may be effected with either a 5a-H- or a SB-H-steroid. Additionally, 14ahydroxylation may be effected by biochemical methods, ass by the action of microorganisms and/or the enzymes formed by them. Suitable systems include enzymes of the type Curvularia, preferably Curvularia lunata, the type Absidia, preferably Absidia regnieri, and especially of the type Helicostylum, preferably Helicostylum piriforme, or the type Mucor, preferably Mucor griseo cyanus.

As indicated above, the various products of this invention possess activity as insect metamorphosis hormones. Thus, the products of this invention may be employed to induce insect metamorphosis at a point in time which is detrimental to the further population of the insect. Because of the hormonal nature of these products, a resistance to their action cannot develop, thus avoiding a significant disadvantage of conventional insecticides. In addition to their metamorphosisinducing activity, the products of this invention possess a profound influence on the cell metabolism in other animals, espcially in warm-blooded animals or crustaceans. For example, by the use of the products of this invention, it is possible to induce the moulting stage in crustaceans, thus rendering them suitable as fish bait. Additionally, the products of this invention can be employed to control crustacean infestation and the damage caused thereby by inducing the moulting stage and exposing the crustaean to natural decimation. F urthermore, the products of this invention have been observed to have central nervous system activity. It is thus readily apparent that the products of this invention have wide utility as pharmaceuticals in horome and veterinary medicine as well as use as agents for the control of insects in agricultural applications. Furthermore, many of the products of this invention serve as intermediates for the manufacture of still other valuable medicinal or agricultural agents.

The products of this invention can be employed in the form of preparations which contain them in admixture with suitable organic or inorganic inert carrier materials such as, for example, water, starch, magnesium stearate, talc, vegetable oils, polyalkylene glycol, or the like.

The following examples are illustrative. For convenience in following the reaction sequences employed, each example is limited to the production of derivatives of a single known starting material, but may illustrate the production of several of the products of this invention as well as the use of one or more of the novel processes of this invention. It is to be understood, however, that these examples are not limited to the specific starting materials or sequences employed, and that other starting materials and reactions known to the art ma be used where desired.

EXAMPLEI From A -cholesten-6-one A. Synthesis of ZB-acetoxy-3,8-hydroxy-5acholestan-6-one To a solution of 2 grams of 5a-A -cholesten-6-0ne in 270 milliliters of glacial acetic acid and 3.7 milliliters of water, there was added 3.2 grams of silver acetate and, with intensive stirring, 1.9 grams of iodine. The resulting reaction mixture was heated with stirring at 45C. for 3 hours, treated with an excess of common salt, stirred for an additional 5 minutes, and then filtered. The deep red filtrate was then evaporated to dryness under vacuum and the residue was taken up in ethyl acetate, washed in sequence with water, thiosulfate solution, and again with water, dried over sodium sulfate, and concentrated to obtain 2B-acetoxy-3B- hydroxy-Sa-cholestan-6-one, melting point 2l7218C. (from methylene chloride/acetonitrile).

B. Synthesis of 2B,3B-dihydroxy-5a-cholestan-6-one An admixture of 2.2 grams of 2B-acetoxy-3B- hydroxy-Sa-cholestan-6-one and 1.1 grams of potassium carbbonate in 200 milliliters of absolute methanol was stirred at room temperature for 15 hours. The reaction solution was thereafter concentrated in vacuum. The residue, aftr being taken up in ethyl acetate, was washed with water, thiosulfate solution, and again with water, dried, and concentrated to obtain 23, 3B- dihydroxy-5a-cholestan-6one, melting point 21 22 l 3C. (from acetonitrile).

C. Synthesis of 2B, 3B-diacetoxyand 23, 3,8- dihydroxy-5B-cholestan-6-one 1. From 28, BB-dihydroxy-Sa-cholestan-6-one a. Acid-catalyzed reaction A solution of 500 milligrams of 2B, 3B-dihydroxy- 5a-cholestan-6-one in 20 milliliters of ethanol and 5 milliliters of 3N hydrochloric acid was heated at boiling for 4 hours. After cooling and dilution with water, the reaction solution was ex- A mixture of 600 milligrams of 2B,3B-dihydroxya-cholestan-6-one, 500 milligrams of potassium hydroxide and milliliters of methanol was heated at reflux for 1 hour. After cooling, the reaction mixture was treated with water and extracted with chloroform. After workup of the extract, there was obtained 2B,3B-dihydroxycholestan-6-one as an approximately equimolar mixture of the 5a-H- and SB-H-isomers.

2. From 2B-acetoxy-3B-hydroxy-5ot-cholestan-6-one a. Acid-catalyzed reaction A solution of 1 gram of ZB-acetoxy-Bfi-hydroxy- Sa-cholestan-G-one in 40 milliliters of ethanol and 10 milliliters of 3N hydrochloric acid was heated at reflux for 4 hours. After coolinng, the reaction mixture was diluted with water and extracted with ethyl acetate. The extract was worked up to yield 2B,3B-dihydroxycholestan- 6-one as an approximately equimolar mixture of the Sa-l-land SB-H-isomers. b. Base-catalyzed reaction A mixture of 1 gram of ZB-acetoxy-3B-hydroxy-5acholestan-o-one and 1 gram of potassium hydroxide in milliliters of methanol was heated at reflux for 2 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. After workup of the extract, there was obtained 2B,3B-dihydroxycholestan- 6-one as an-approximately equimolar mixture of the Sa-H- and SB-H-isomers. 3. Isolation of 2B-diacetoxy-Sflcholestan-6-one A solution of 1 gram of ZB-dihydroxycholestan-- one-S-H-isomeric mixture produced as described above in 20 milliliters of acetic anhydride and 10 milliliters of pyridine was allowed to stand overnight at room temperature. After the addition of ice and extraction with chloroform, the extract was washed first with dilute hydrochloric acid and then water. The extract was then dried over sodium sul-' fate and concentrated in vacuum to yield 23,33- diacetoxy-SB-cholestan-6-one, melting point 148-l49C. (from petroleum ether). 4. Isolation of 2B,3B-dihydroxy-5B-cholestan-6-one A solution of 1 gram of 2B,3B-diacetoxy-5B- cholestan-G-one in 100 milliliters of absolute methanol was treated with 0.5 gram of potassium carbonate and stirred overnight at room temperature. The resulting reaction mixture was poured into water and extracted with chloroform. After workup of the extract, there was obtained 28,35- dihydroxy-SB-cholestan-done, melting point l67l68C. (from acetonitrile and acetone). D. Synthesis of 2B,3B-isopropylidenedioxy-SB- cholestan-6-one There was added 7 grams of calcium chloride to a solution of 1.3 grams of 23,3B-dihydroxy-Soz-cholestan- 6-one in 70 milliliters of acetone containing 1 percent hydrochloric acid. The resulting reaction mixture was stirred for 16 hours at room temperature and then poured into water. After extraction with ethyl acetate, washing the extract with water, dilute sodium bicarbonate solution and again with water, drying the extract and evaporation of the solvent, there was obtained 28,- 3B-isopropylidenedioxy-SB-cholestan-fi-one. melting point 171C. (from acetonitrile).

EXAMPLE II From 3B-hydroxy-N-cholesten-6-one A. Synthesis of ZB-acetoxy-3B-hydroxy-5a-N- cholesten -6-one A mixture of ll grams of 3B-hydroxy-5a-N- cholesten-6-one, 15 grams of p-toluenesulfonic acid, and 250 milliliters of pyridine was stirred at room temperature for 24 hours and then poured into ice water. The precipitate which formed was filtered off and dissolved in methylene chloride. The resulting solution was washed with water, dried over sodium sulfate and evaporated to dryness. Upon recrystallization of the residue from diisopropyl ether, there was obtained 33- tosyloxy-Sa-N-cholesten-G-one, melting point l53l54C.

A mixture of 4 grams of 3B-toxyloxy-5a-A cholesten-6-one, 1 gram of lithium bromide, 1.5 grams of lithium carbonate, and 200 milliliters of dimethylformamide was heated at 120C. for 5 hours. After cooling, the reaction mixture was poured into ice water and weakly acidified with hydrochloric acid. The resulting precipitate was filtered off and dissolved in methylenechloride. The resulting solution was washed with water, dried and concentrated to yield Sat-A- cholestadien--one.

The thus-produced 5a-A -cholestadien-6-one was dissolved in 250 milliliters of acetic acid at 60C. Thereafter, there was added in sequence 3.9 milliliters of water, 3.1 grams of silver acetate, and 2 grams of finely ground iodine. The resulting reaction mixture was heated at 60C. with vigorous stirring for 5 hours. After treating with an excess of common salt and stirring for an additional 5 minutes, the reaction mixture was filtered. The deep red filtrate was concentrated to dryness under vacuum. The residue was taken up in ether and the ether solution was washed with water, bicarbonate solution, and again with water, and then dried and concentrated. After recrystallization of the residue from diisopropyl ether, there was obtained 2B-acetoxy-3B-hydroxy-5a-A cholesten--one, melting point 2l52l7.5C.

B. Synthesis of 2B, 3B-hydroxy-Sa-N-cholesten- 6-one A mixture of 1 gram of ZB-acetoxy-3B-hydroxy-5a- A -cholesten-6-one and 1 gram of potassium carbonate in milliliters of methanol was stirred at room temperature for 40 minutes After pouring the resulting reaction mixture into water, the precipitate which had formed was filtered off and dissolved in methylene chloride. Workup of this solution gave 23,38- dihydroxy-Sa-N-cholesten-G-one, melting point 208210C. (from acetone).

C. Synthesis of 2B, 3B-diacetoxyand 23,36- dihydroxy-Sfl-A -cholesten-o-one 1. From 25', 3,8-dihydroxy-5a-A -cholesten-6one a. Acid-catalyzed reaction A mixture of 500 milligrams of ZBJB-dihydroxy-Soz- N-cholesten--one in 25 milliliters of ethanol and 5 milliliters of 3N hydrochloric acid was heated at boiling for 20 hours. After cooling, the mixture was poured into ice water and the precipitate which formed was separated and taken up in methylene chloride. The organic solution was washed with water, dried with sodium sulfate and concentrated in vacuum. On recrystallization of the residue from diisopropyl ether, there was obtained 28,33- dihydroxy-A -cholesten-6-one as an approximately equimolar mixture of the Sa-H- and SB-I-I-isomers. b. Base-catalyzed reaction A mixture of 500 milligrams of 23,3/3-dihydroxy- 5a-A -cholesten-6-one, 500 milligrams of potassium hydroxide and 20 milliliters of methanol was heated under reflux for 2 hours. After cooling, pouring the reaction mixture into ice water and workup of the resulting precipitate as described above, there was obtained 26,313- dihydroxy-N-choleston-6-one as a mixture of the Sa-H- and SB-H-isomers. 2. From 2B-acetoxy-3B-hydroxy-5a-N-cholesten- 6-one a. Acid-catalyzed reaction A mixture of 1 gram of 2,8-acet0xy-3B-hydroxy-5a- A -cholesten-6-one in 50 milliliters of ethanol and 10 milliliters of 3N hydrochloric acid was heated at boiling for 20 hours. After cooling and pouring the reaction mixture into ice water, the precipitate which had formed was separated and taken up in methylene chloride. After workup of the organic solution, there was obtained 23,38- dihydroxy-N-cholesten-6-one as a mixture of the Sa-H- and SB-l-I-isomers. b. Base-catalyzed reaction A mixture of 500 milligrams of 2B-acetoxy-3B- hydroxy-Sa-A -cholesten-6-one and 500 milligrams of potassium hydroxide in 30 milliliters of methanol was heated under reflux for 4 hours. After cooling the reaction mixture and pouring it into ice water, the precipitate which had formed was separated out and worked up as described above to obtain 2,8,3B-dihydroxy-N- cholesten-6-one as a mixture of the Sa-H- and SB-H- isomers.

3. Isolation of 23,3B-diacetoxy-SB-N-choleston- 6one A solution of 1 gram of 2,8,3B-dihydroxy- A cholesten-6-one-5-H-isomeric mixture produced as de-' scribed above in 30 milliliters of acetic anhydride and milliliters of pyridine was held at room temperature for 4 hours. The resulting reaction mixture was poured into ice water and extracted with methylene chloride. The organic extract was washed with dilute sulfuric acid and water, dried and concentrated. After recrystallization from pentane, there was obtained 23,38-

diacetoxy-SB-A -cholesten-6one, melting point 4. Production of 2B,3,8-dihydroxy-SB-cholesten- 6-one A mixture of 1 gram of 2B,3B-diacetoxy -5B-A cholesten-6-one, 1 gram of potassium carbonate, and 100 milliliters of methanol was stirred at room temperature for 40 minutes. The resulting reaction mixture was poured into water and the aqueous mixture was extracted with methylene chloride. The organic phase was washed with water, dried, and concentrated to obtained 2,8,3B-dihydroxy-5B- A -cholesten-6-one, melting point 207209C. (from diisopropyl ether).

D. Synthesis of 23,3B-isopropylidene-SB-N- choleston-6-one A solution of 400 milligrams of 2B,3B-dihydroxy-5B- A -cholesten-6-one in 100 milliliters of acetone was cooled to 0C., treated with one drop of boron trifluoride etherate and held at 0C. for 15 minutes. The resulting reaction mixture was poured into water, extracted with methylene chloride, and the methylene chloride phase was washed with water, dried and concentrated to obtain 28,35- isopropylidenedioxy-SB-N-cholesten-6-one, melting point l63l63.5C. (from methanol). E. Synthesis of 23,33, l4a-trihydroxy -5B-N- cholesten-6-one 1. Introduction of the l4a-hydroxy group followed by isomerization Employing procedures similar to those described in Example IA(3), 3,8-acetoxy-3B-hydroxy-N-cholesten- 6-one was acetylated to 2B,3B-diacetoxy-5a-A cholesten-6-one, melting point 196-198C. (from methanol). Employing techniques similar to those described in Example IV below, this product was reacted with selenium dioxide in dioxane to produce 23,313- diacetoxy-14a-hydroxy-5a-A -cholesten-6-one, melting point 23l-232C. (from methanol). Employing procedures similar to those described in Example [C(2), the thus-obtained product was isomerized with potassium hydroxide in methanol. After workup there was obtained 23,33,14a-trihydroxy-5,B-N-cholesten- 6-one, melting point 207209C. (from ether/hexane). In the manner described in Example [C(3) above, the above-obtained 23,313,l4a-trihydroxy-compound was reacted with acetic anhydride in pyridine to produce 2/3,3B-diacetoxy-l4a-hydroxy-5B-N-cholesten-6-one, melting point l89l9lC. (from isopropyl ether).

2. Simultaneous l4a-hydroxylation and isomerization A solution of 1 gram of 2B-acetoxy-3B-hydroxy-5oz- A -cholesten-6-one in 100 milliliters of absolute dioxane was heated at C. To this solution was added two l-gram portions of freshly sublimed selenium dioxide over a 30-minute period. The resulting mixture was heated an additional 2 V2 hours at 80C. with stirring. After filtration of the reaction mixture, the filtrate was concentrated under vacuum and mixed with water. The precipitate which formed was separated and dissolved in methylene chloride. The resulting organic solution was washed with water, dried over sodium sulfate and evaporated to obtain 2B-acetoxy-3B,l4adihydroxy-SB-N-cholesten-6-one, melting point 260-261C. (from diethyl ether).

EXAMPLE III From BB-acetoxy-A -ergostadien-6-one A. Synthesis of 2B-acetoxy-3/3-hydroxy-5cit-A ergostadien-6-one A mixture of 11.7 grams of 3B-acetoxy-A -5aergostadien-6-one, 11.7 grams of potassium carbonate and 2 liters of methanol was heated at boiling for 30 minutes. The resulting reaction mixture, after cooling, was poured into water and the organic phase was washed, dried, and concentrated.

The crude saponification product, in admixture with 200 milliliters of pyridine and 13.5 grams of ptoluenesulfonyl chloride, was held at room temperature for 24 hours. After dilution of the reaction mixture with water, the precipitate which had formed was separated off and dissolved in methylene chloride. The organic solution was washed, dried and concentrated to yield 3B-tosyloxy-Af' -5a-ergostadien-6-one which, after crystallization from diisopropyl ether, melted at 148149C.

A mixture of 2.2 grams of 3B-tosyloxy-A -aergostadien-6-one in milliliters of dimethylaniline was heated at 200C. for minutes. After cooling, the reaction solution was poured into dilute sulfuric acid, and the precipitate which formed was filtered off by suction and taken up in chloroform. The organic solution was washed until neutral, dried and concentrated to yield A -5a-ergostadien-6-one.

After dissolving the crude product in 130 milliliters of acetic acid at 45C., there was successively added 2.1 milliliters of water, 1.8 grams of silver acetate and 1.09 grams of finely powdered iodine. The resulting mixture was heated with vigorous stirring at 45C. for 50 minutes. After the addition of an excess of common salt, the reaction mixture was stirred for an additional 5 minutes, filtered and the filtrate concentrated to dryness in vacuum. The residue was purified by preparative thin layer chromatography, and after recrystallization from diisopropyl ether, there was obtained 23- acetoxy-3B-hydr0xy-A -5a-ergostadien-6-one, melting point 208-2l0C.

B. Synthesis of 2B,3B-dihyclroxyand 25,33

diacetoxy-5B-66 -ergosta lien-6-one A solution of 2,1 grams of 2B-acetoxy-3B-hydroxy- A- -5a-ergostadien-6-one in 100 milliliters of ethanol and 20 milliliters of 3N hydrochloric acid was heated at boiling for 20 hours. After cooling, the reaction mixture was diluted with water and the precipitate which formed was separated and taken up in methylene chloride. The organic solution was washed with water, dried over sodium sulfate and concentrated in vacuum to obtain 2B,3B-dihydroxy-A -5B-ergostadien-6-one as an oil.

The diol was acetylated at room temperature for 16 hours by reaction with 5 milliliters of pyridine and 2.5 milliliters of acetic anhydride. The resulting reaction mixture was diluted with water and the precipitate which formed was filtered off and dissolved in methylene chloride. After washing until neutral, the organic solution was dried and concentrated in vacuum to yield 2B,3B-diacetoxy-A -5B-ergostadien-6-one, melting point l48l50C. (from acetone/hexane).

C. Synthesis of 2B,3B-diacetoxy-l4a-liydroxyhydroxy-SB-A" -ergostadien--one A solution of 5.8 grams of 2B-acetoxy-3B-hydroxy- 5B-A -ergostadien-6-one in 80 milliliters each of absolute pyridine and acetic anhydride was allowed to stand at room temperature overnight and then was decomposed with ice water, and extracted with chloroform. The extracts were washed until neutral and evaporated to yield 2,8,3B-diacetoxy-5a-A -ergostadien- 6-one, melting point 195196C. (from methanol).

A solution of 3 grams of 2B,3B-diacetoxy-5a-A ergostadien-G-one in 120 milliliters of absolute dioxane was heated to 80 in an inert atmosphere. After the addition of 6.1 grams of selenium dioxide, the reaction mixture was stirred for 15 minutes, filtered, diluted with water and extracted with ether. The extract was washed with water and the solvent evaporated. The residue was chromatographed on 100 grams of alumina, using benzene containing 10 percent of ether as the eluting agent, to obtain 2B,3B-diacetoxy-l4a-hydroxy- Set-A -ergostadien-6-one, melting point after recrystallization from isopropyl ether, 226-227C.

A mixture of 1.3 grams of 213,3;8-diacetoxy-l4ahydroxy-5a-A7,22-ergostadien-6-one, 60 milliliters of methanol, 5 milliliters of water and 0.5 gram of potassium carbonate was heated at boiling overnight in an inert atmosphere. The reaction mixture was then diluted with water and extracted with chloroform. The extract was washed until neutral, dried and evaporated.

-The crude reaction product was reacted with acetic an hydride in pyridine according to the procedure described in Example IC(3). After workup, the crude product was chromatographed on 30 grams of alumina. Elution with benzene-ether (1:1) yielded 23,33- diacetoxyl 4a-hydroxy-5B-A -ergostadien-o-one, melting point 202203C. (from methanol).

in an alternative procedure a mixture of 1 gram of 2- B-acetoxy-3B-hydroxy-Sa-A -ergostadien-6-0ne, 2 grams of selenium dioxide and 30 milliliters of absolute dioxane is stirred at room temperature for 24 hours. The reaction mixture was filtered and the filtrate was stirred with 0.5 gram of deactivated Raney nickel. After filtration and evaporation, there was obtained 2- B-acetoxy-3 B, l 4a-dihydroxy-5a-A ergostadien- 6-one, melting point 254-256C. (decomp) (from acetonitrile).

A solution of 600 milligrams of 2B-acet0xy-3B,l4adihydroxy-5a-A -ergostadien-6-one in 45 milliliters of methanol and 5 milliliters of water was treated with 250 milligrams of potassium carbonate according to the procedure described above. After workup, there was obtained 213,3B-diacetoxy-l4a-hydroxy-5B-A ergostadien-6-one, which is identical with the product produced as described above.

D. Synthesis of (22R), 2B,3B,14a,22,25- pentahydroxy-5B-A -cholesten-6-one (ecdyson A solution of 4 grams of 2B,3B-diacetoxy-5a-A ergostadien-6-one (produced as described in part C above) in 750 milliliters of methylene chloride and 500 milliliters of methanol was treated at -C. over a minute period with 10 millimols of ozone which was supplied in an oxygen stream. After the addition of 15 milliliters of trimethoxyphosphine, the mixture was stirred for 30 minutes, then decomposed with water and extracted with ether. Processing of the ether extracts afforded a crude product which was quickly chromatographed on alumina to obtain (20S),2B,3B- diaeetoxy-ZO-formyl-Sa-A -pregnen-6-one, melting point 21l-212C. (from methylene chloride-ether).

To a solution of ethyl magnesium bromide (prepared from 2 grams of magnesium and 6.4 milliliters of ethyl bromide in milliliters of ether), there was added dropwise a solution of 16 milliliters of 2-methyl-2-tetrahydropyranyl0xy-3-butyne in 100 milliliters of tetrahydrofuran. The reaction solution was stirred for 30 minutes at room temperature and then added dropwise with stirring to a solution of 4.7 grams of (20S),2B,3/3- diacetoxy-20-formyl-5a-N-pregnen-o-one in 200 milliliters of tetrahydrofuran at l0C. The temperature of the reaction mixture was allowed to rise to 0C., whereupon the mixture was decomposed by the addition of ammonium chloride solution. Extraction with ether afforded a crude product which was chromatographed on 200 grams of alumina. The fractions obtained by elution with 2 liters of benzene-petroleum ether (1:1) were discarded. The product was then eluted with chloroform containing 10 percent of methanol and again chromatographed on grams of alumina. After removal of undesired by-products, the (22R),2B,3B- diacetoxy-Z2hydroxy-25-(tetrahydropyran-Z-yloxy)- 5a-N-cholesten-Z3-yn-6-one was eluted with benzene and benzene containing 1 percent of ether. Melting point 188C. (from isopropyl ether).

A solution of 1 gram of (22R), 2B,3,B-diacetoxy-22- hydroxy-25-(tetrahydropyran-2-yloxy)-5a-A -cholesten-23-yn-6 one in 50 milliliters of methanol was hydrogenated in the presence of 200 milligrams of prehydrogenated platinum until the uptake of 75 milliliters of hydrogen. After workup there was obtained (22R),- 2,8,3B-diacetoxy-22-hydroxy-25-(tetrahydropyran-2- yloxy)-5a- -cholesten-6-one, melting point 155156C. (from isopropyl ether).

A solution of 3 grams of (22R),2B,3B-diacetoxy-22- hydroxy-25-(tetrahydropyran-Z-yloxy)-5a-A cholesten-6-one in 150 milliliters of absolute dioxane was stirred with 6 grams of selenium dioxide at 20C. for 15 hours. The suspension was filtered, and 1 gram of deactivated Raney nickel was added to the filtrate. After stirring for 30 minutes and filtration, the solution was diluted with chloroform, washed with water and evaporated. Recrystallization of the residue from ether afforded (22R ,2B,3B-diacetoxy- 1 4a,22-dihydroxy- 25-(tetrahydropyran-Z-yloxy)-5a-A -cholesten-6-one, melting point l94l95C.

A solution of 1 gram of (22R), 2B,3B-diacetoxy-14a, 22-dihydroxy-25-(tetrahydorpyran-2-yloxy)-5a-A cholesten-6-one and 200 milligrams of potassium carbonate in 20 milliliters of methanol was heated to reflux for 2 hours. The reaction mixture was diluted with 200 milliliters of ethyl acetate, washed with saturated brine, dried and evaporated. The residue was dissolved in 16 milliliters of methanol, and allowed to stand with 4 milliliters of 2N hydrochloric acid for 15 minutes at room temperature. The mixture was then neutralized with 8 milliliters of 1N sodium hydroxide and, after the addition of ethanol, evaporated to dryness. The residue was dissolved in tetrahydrofuran and the resulting solution was filtered and evaporated. Recrystallization from methyl ethyl ketone afforded (22R),2B,3B,14o ,2- 2,25-pentahydroxy-5B-A -cholesten-6-one, melting point 233C. (decomp.). Melting point after further recrystallization from methanol-acetone, 241C. (decomp.).

E. Synthesis of 3B-acetoxy-22-hydroxy-25- (tetrahydropyran-Z-yloxy)-5a-A -cholesten-23-yn- 6-one Employing procedures similar to those described above, 3/3-acetoxy-A -5a-ergostadien-6-one was subjected to ozonolysis to produce 3B-acetoxy-20-formyl- 5a-A -pregnen-6-one.

To an ethyl magnesium bromide solution [produced from 244 milligrams of magnesium and 0.84 milliliters of ethyl bromide in 15 milliliters of ether], there was added dropwise a solution of 1.93 milliliters of 2- methyl-Z-tetrahydropyranyloxy-3-butyne in 10 milliliters of tetrahydrofuran, and the resulting mixture was stirred for 1 hour at room temperature. The resulting solution was cooled to 5C. and there was added a solution of 386.5 milligrams of 3,8-acetoxy-20-formyloz-A -pregnen-6-one in milliliters of tetrahydrofuran. The resulting mixture was stirred for 45 minutes and then mixed with saturated ammonium chloride solution. After taking the product up in ether, it was washed with saturated salt solution, dried and evaporated. After chromatographing on silica gel, there was obtained 3B-acetoxy-22-hydroxy-25-(tetrahydropyran- 2-yloxy)-5a-A -cholesten-23-yn-6-one, melting point 175l78C. (from hexane/ether).

EXAMPLE 1V From methyl A. Synthesis of methyl oxidopregnane-20-carboxylate To a mixture of 331 grams of methyl 3,3- ethylenedioxy-A -pregnene-20-carboxylate [K. Morita, Chem, Abs., 54, 4679 (1960)], grams of potassiumacetate, 166 grams of sodium sulfate, and 3,300 milliliters of methylene chloride, there was added dropwise under ice cooling 275 milliliters of 40 percent peracetic acid. The resulting reaction mixture was stirred at 22C. for 2 hours, treated with water and diluted with methylene chloride. The methylene chloride phase was separated, washed with sodium carbonate solution and water, dried over sodium sulfate and evaporated in vacuum to yield the desired 5,6-oxido-compound as an isomeric mixture.

B. Synthesis of SB-I-l-compounds via 5,6-opoxides 1. Synthesis of methyl 2B,3B-dihydroxy-5B,6B-oxidopregnane-ZO-carboxylate The epoxide mixture as described in A above was dissolved in 2,500 milliliters of tetrahydrofuran, treated at 05C. with 690 milliliters of 3N perchloric acid and allowed to stand at 5C. for 16 hours. The resulting solution was stirred into 30 liters of ice water, neutralized and the precipitated diol was filtered off by suction, washed and dried. After recrystallization from acetone, there was obtained methyl 5a,6B-dihydroxypregnan-3- one-20-carboxylate, melting point 233-235C.

To a solution of 10 grams of the Soz,6B-diol in 128 milliliters of tetrahydrofuran there was added dropwise over 8 minutes with ice cooling a solution of 1.365 milliliters of bromine in 15 milliliters of glacial acetic acid. After stirring for an additional 5 minutes the reaction solution was poured into ice water containing sodium acetate and then extracted with methylene chloride. The methylene chloride solution was washed until neutral, evaporated in vacuum at 30C. and the residue was triturated with isopropyl ether to yield methyl 2abromo-Sa,6B-dihydroxypregnan-3-one-20- carboxylate.

To a mixture of 8.9 grams of the thus-obtained 2abromo-compound in 80 milliliters of dry tetrahydrofuran, there was added at 05C. a solution of 9.6 grams of lithium tri(tert.-butoxy) aluminum hydride in 50 milliliters of tetrahydrofuran. The resulting mixture was stirred into a sulfuric acid/ice water mixture, extracted with acetic ester, washed until neutral and evaporated in vacuum. Upon recrystallization from isopropyl either and then from acetone there was obtained methyl 2a-bromo-36,5a,6B-trihydroxypregnane-20- carboxylate, melting point 217218C. (dec.).

A solution of 8.5 grams of the thus-obtained triol in milliliters of glacial acetic acid was treated with 17 milliliters of acetic anhydride and 850 milligrams of p-toluenesulfonic acid and then allowed to stand at room temperature for 48 hours. The resulting solution was stirred into ice water and the resulting precipitate was filtered off by suction, washed with water and dried. After recrystallization from isopropyl ether, there was obtained methyl 2a-bromo-3B,5a,6B- triacetoxypregnane-20-carboxylate, melting point 211213C. (dec.).

A solution of 7.1 grams of the triacetate in milliliters of glacial acetic acid was heated under reflux for 22 hours with 5 grams of silver acetate and 3 milliliters of water. The precipitate was filtered off by suction and the filtrate was poured into ice water. The reaction product which precipitated was filtered off by suction, washed until neutral and dried. After chromatograping on silica gel and recrystallization from acetone/hexane,

3,3-ethlenedioxy-5,6-

there was obtained methyl 2/3,3B,5a,6,8- tetraacetoxypregnane-20-carboxylate, melting point 202-203C.

A solution of 15.74 grams of the tetraacetate in 315 milliliters of methanol and 79 milliliters of water was refluxed for 2 hours with l 1.8 grams of potassium hydroxide and then neutralized with acetic acid. After vacuum distillation to remove the methanol, the residue was treated with 200 milliliters of water. The reaction product which precipitated was filtered ofi by suction, washed with water and dried. The crude carboxylic acid thus obtained was allowed to stand at room temperature for one hour in 200 milliliters of methylene chloride and 200 milliliters of etheric diazomethane solution (manufactured from 30 grams of nitrosomethylurea). After evaporation in vacuum, chromatography of the residue on silica gel and recrystallization from acetone/hexane, there was obtained methyl 23,3B-dihydroxy-5,6B-oxidopregnane-20-carboxylate, melting point 185.5l86C.

2. Synthesis of methyl 2B,3B-isopr0pylidenedioxy- 5,6B-oxidopregnane-ZO-carboxylate A mixture of 300 milligrams of the tetraacetate pro-' duced as described above in 6 milliliters of a 10 percent methanolic potassium hydroxide solution was allowed to stand at room temperature for 16 hours. After acidification with 1N hydrochloric acid, the solution was diluted' with ethyl acetate, washed until neutral and evaporated. The residue was admixed with 30 milliliters of etheric diazomethane solution (manufactured from 2 grams of nitrosomethylurea) and allowed to stand for 2 hours. The resulting solution was evaporated under vacuum and the residue was purified by preparative thin layer chromatography to obtain methyl 2B,3,8,6B- trihydroxy-Sa-acetoxypregnane--carboxylate, melting point 22022l.5C.

A mixture of 2.55 grams of the trihydroxymonoacetoxy compound, 0.4 milliliters of boron trifluoride etherate, and 100 milliliters of dry acetone was allowed to stand at room temperature for minutes. After the addition of 2 milliliters of pyridine, the reaction mixture was evaporated under vacuum and the residue was precipitated with ice water. After filtering off the precipitate by suction, it was dried and then recrystallized from acetone/hexane to yield methyl 2B,3B-'

isopropylidenedioxy-Sa-acetoxy-6B-hydroxypregnane- 20-carboxylate, melting point 192.5-l93C.

A mixture of 600 milligrams of this product, 48 milliliters of methanol, 12 milliliters of water, and 1.8 grams of potassium hydroxide was heated under reflux for 3% hours. The mixture was then stirred into ice water, acidified with hydrochloric acid, and the resulting precipitate was filtered off by suction, washed until neutral and dried. The crude acid was dissolved in 5 milliliters of tetrahydrofuran and allowed to stand for 2 hours with 30 milliliters of etheric diazomethane solution. The resulting solution was evaporated under vacuum and the residue was fractionated by preparative thin layer chromatography to yield methyl 213,33- isopropylidienedioxy-S,6B-oxidopregnane-20 -carboxylate melting point 149.5150C. and methyl 23,313- isopropylidenedioxy-Sa,6B-dihydroxypregnane-ZO -carboxylate, melting point 266267C.

3. Synthesis of methyl 2B,3B-isopropylidenedioxy- 5,a-oxidopregnane-20-carboxylate A mixture of 200 milligrams of the 5a,6B-d1iol produced as described above, 5 milliliters of pyridine and 0.5 milliliter of methanesulfonic acid chloride was stirred at 5C. for 16 hours. The resulting mixture was poured into ice water, filtered by suction and dried. The crude 6-mesylate in admixture with 10 milliliters ofpyridine, l0 milliliters of water, and 3 grams of sodium bicarbonate was heated under reflux for 30 minutes. The resulting mixture was stirred into water and extracted with methylene chloride. The methylene chloride solution was washed with dilute hydrochloric acid and water and then evaporated. After recrystallization from acetone, there was obtained methyl 213,38- isopropylidenedioxy-S ,6a-oxidopregnane-20- carboxylate, melting point l99201C. 4. Synthesis of methyl 2B,3B-dihydroxyand 23,313-

diacetoxy-5B-pregnan-6-one-20-carboxylates a. From methyl 2B,3B-dihydroxy-5,6B-oxidopregnane-ZO-carboxylate A mixture of 100 milligrams of methyl 23,33-

dihydroxy-S,6B-oxidopregnane-ZO-carboxylate, l0 milliliters of benzene, and 0.1 milliliter of boron trifluoride etherate was stirred at room 1 temperature for 20 hours. After the addition of 0.5 milliliter of pyridine, the mixture was diluted with ethyl acetate, washed in sequence with water, 1N hydrochloric acid, and again with water, dried and evaporated. From the residue there was isolated by preparative thin layer chromatography methyl 23,3,B-dihydroxy-5/3-pregnan-6- one-20-carboxylate, which after recrystallization from isopropyl ether/methylene chloride, melted at l8l.5-l83C. b. From methyl 213,3B-isopropylidenedioxy-S,6B-

oxidopregnane-ZO-carboxylate A mixture of 100 milligrams of methyl 2 3,38-

isopropylidenedioxy-S,6B-oxidopregnane-20- carboxylate, 5 milliliters of acetone and 0.2 milliliter of boron trifluoride etherate was stirred at room temperature for 1 hour and then treated with 0.5 milliliter of pyridine and evaporated under vacuum. The residue was heated on a steam bath for 2 hours in admixture with 10 milliliters of 61 percent acetic acid and 1 drop of 2N sulfuric acid. The resulting mixture was stirred into water and extracted with chloroform. The extract was washed with water, evaporated and the residue was recrystallized from isopropyl ether to yield methyl 2B,3B-dihydroxy-5fipregnan-6-one-20-carboxylate identical with the compound produced in part (a) above. c. Synthesis of methyl 25,3,8-diacetoxy-5fipregnan-6-one-20-carboxylate A mixture of 200 milligrams of methyl 2B,3B- dihydroxy-5B-pregnan-6-one-20-carboxylate, 2 milliliters of glacial acetic acid, 0.4 milliliter of acetic anhydride, and 20 milligrams of p-toluenesulfonic acid was allowed to stand at 20C. for 24 hours. The resulting mixture was stirred into ice water and extracted with methylene chloride. The methylene chloride solution was washed until neutral, concentrated and recrystallized from isopropyl ether to yield methyl 25,33- diacetoxy-SB-pregnan-6-one-20-carboxylate, melting point 176.5-l77.5C. 5. Synthesis of methyl 2B,BB-isopropylidenedioxy- SB-pregnan--one-ZO-carboxylate a. From methyl 2,8,3B-is0propylidenedioxy-5,66-

oxidopregnane-20-carboxylate A mixture of 200 milligrams of methyl 23,36-

isopropylidenedioxy-S,6a-oxidopregnane-20- carboxylate, 10 milliliters of benzene, and 0.2 milliliter of boron trifluoride etherate was stirred for hours at room temperature. After workup as described in part (4)(a) above, there was recovered methyl 2B,3,8-isopropylidenedioxy-SB- pregnan-6-one-20-carboxylate, melting point l96.5l98C. (from isopropyl ether).

b. From methyl 28,3B-dihydroxy-5B-pregnan-6- one-20-carboxylate A mixture of 150 milligrams of methyl 2B,3,B-

dihydroxy-SB-pregnan-6-one-20-carboxylate, 10 milliliters of acetone, and 0.03 milliliter of boron trifluoride etherate was allowed to stand at room temperature for 30 minutes. After workup as described above, there was obtained methyl 23,33- isopropylidenedioxy-SB-pregnan-6-one-20- carboxylate identical to that produced in part (a) above.

C. Synthesis of SB-l-l-compounds via isomerization of Sa-l-l-compounds 1. Synthesis of methyl (S),2B, 3B-diacetoxy-5apregnan-6-one-20-carboxylate An epoxide mixture produced in the manner described in A above was dissolved in 2500 milliliters of tetrahydrofuran, treated with 690 milliliters of 3N perchloric acid and heated under reflux for 3.5 hours. The resulting solution was stirred into liters of ice water, neutralized and the precipitated dione filtered off by suction. After washing, drying, and recrystallization from ethyl acetate, there was obtained methyl (20S),5a-pregnane-3,6-dione-20- carboxylate, melting point 2122l4C.

To a mixture of 37.45 grams of the 3,6-dione in 800 milliliters of tetrahydrofuran, there was added dropwise with ice cooling a solution of 5.33 milliliters of bromine and 4.9 grams of potassium acetate in 50 milliliters of glacial acetic acid. The resulting reaction solu-' tion was poured into ice water containing sodium acetate. The precipitate which formed was filtered off by suction and recrystallized from methanol to yield methyl (20S ,2a-bromo-5 oz-pregnane-3 ,6-dione-20- carboxylate, melting point l6l-l62C. (dec.).

A solution of 28 grams of the 2a-bromo-3,6-dione in 240 milliliters of tetrahydrofuran was diluted at 05C. with a solution of 33.8 grams of lithium tri(tert.- butoxy)aluminum hydride in 160 milliliters of tetrahydrofuran. The resulting mixture was stirred into a sulfu-,

ric acid-ice water mixture and the precipitate which formed was filtered off by suction and recrystallized from ethyl acetate to yield methyl (20S), 2a-bromo- 3B-hydroxy-5a-pregnan-6-one-20-carboxylate, melting point 21 l-2l2C.

A mixture of 19.4 grams of the resulting alcohol in 80 milliliters of pyridine and 40 milliliters of acetic anhydride was allowed to stand at room temperature for 20 hours. The resulting mixture was stirred into ice water and the precipitate which formed was filtered off by suction and recrystallized from acetone/hexane to yield methyl (20S),Za-bromo-Sa-pregnan-6-one-20- carboxylate, melting point l96l97C.

A mixture of 81.2 grams of the product acetate, 800 milliliters of glacial acetic acid, 16.2 milliliters of water and 50 grams of silver acetate was heated under reflux for 20 hours. The precipitate which formed was filtered off by suction and the filtrate was stirred into ice water.

The resulting precipitate was filtered off by suction, washed until neutral, and dried. After recrystallization from methanol, there was obtained 58.6 grams of methyl (20S ,2,B,3B-diacetoxy-pregnan-6-one-20- carboxylate as a mixture of 5aand SB-isomers. After fractional crystallization from methylene chlorideisopropyl ether and methylene chloride-methanol, there was recovered the Sol-isomer, melting point 222.5224C., and the SB-isomer, melting point l 76.5-l 77.5C.

2. Synthesis of methyl 2B,3B-diacetoxy-5a-A pregnan-6-one-20-carboxylate A mixture of 29.3 grams of the mixture of Sa-H- and SB-l-l-isomers produced as described above in 500 milliliters of glacial acetic acid was treated dropwise with 3.3 grams of bromine in glacial acetic acid and the resulting mixture was stirred at 50C. for 2 hours. The reaction mixture was then stirred into an ice/potassium acetate solution and the precipitate which formed was filtered off by suction, washed until neutral, and dried. After recrystallization from acetone/hexane, there was obtained methyl (20S),2,B,3B-diacetoxy-7a-bromo-5- pregnan-6-one-20-carboxylate, melting point 152l53C.

A mixture of 38 grams of the 7a-bromo compound, 10.3 grams of lithium carbonate, 6.2 grams of lithium bromide, and 380 milliliters of dimethylformamide was heated at l20l25C. for 4.5 hours under a nitrogen atmosphere. After filtration to remove undissolved lithium salts, the filtrate was stirred into ice water. The precipitate which formed was filtered off by suction, dried and chromatographed on silica gel. After recrystallization from isopropyl ether/methylene chloride, there was obtained methyl (2OS),2B,3B-diacetoxy-5a- A -pregnen-6-one-20-carboxylate, melting point 195196C.

3. Synthesis of methyl 2,8,3B-dihydroxyand 28,35-

diacetoxy-SB-N-pregnen-6-one-20-carboxylate A solution of 500 milligrams of methyl 2,8,3/3-

diacetoxy-Sa-A -pregnen-6-one-20-carboxylate, 20 milliliters of ethanol and 1.5 milliliters of 3N hydrochloric acid was heated under reflux for 20 hours and worked up as described above. The resulting mixture of 5aand SB-l-lisomers was then acetylated as described above to yield methyl (20S- ),2,8,3B-diacetoxy-SB-A -pregnen-6-one-20- carboxylate, melting point 194.5195.5C. Hydrolysis of this product as previously described yields the corresponding methyl 2B,3B-dihydroxy-5,B-H-

isomer, melting point 224226C. (from acetone/- hexane).

4. Synthesis of methyl 2B,3B,l4a-trihydroxyand 2,8,3B-diacetoxy- 1 4a-hydroxy -5B-A -pregne n- 6-one-20-carboxylate A mixture of 1.5 grams of methyl (20S),2B,3B- diacetoxy-5a-N-pregnen-6-one-20-carboxylate, 1.5 grams of selenium dioxide and 107 milliliters of dioxane was stirred at C. for 30 minutes. After filtering off the insoluble selenium, the filtrate was stirred into ice water. The precipitate which formed was filtered off by suction, washed until neutral and dried. After recrystallization from methanol, there was obtained methyl (20S),2B,3B- diacetoxy-l4a-hydroxy-5a-A -pregnen-6-one-20- carboxylate, melting point 248-249.5C.

A 300-milligram portion of the resulting product was heated under reflux in 10 milliliters of methanol and 0.5 grams of potassium hydroxide for 1 hour and then worked up as described above. After recrystallization from acetone, there was obtained methyl (2OS),2B,3/3,- l 4a-trihydroxy-SB-A -pregnen-6-one-20-carboxylate,

rnelting point 238240C.

Employing procedures similar to those described above, 30 milligrams of the 2B,3B,14a-trihydroxy compound were acetylated with l milliliter of pyridine in 0.5 milliliter of acetic anhydride. After recrystallization from acetone/hexane, there was obtained methyl (20S- ),2B,3fi-diacetoxyl 4a-hydroxy-5B-N-pregnen-6-one- 20-carboxylate, melting point 24l-242C.

5. Synthesis of (22R),2,8,3B,l4a,22,25-

pentahydroxy-SB-A -cholesten-6-one (ecdyson) A mixture of l grams of methyl (20S),2,8,3B-

diacetoxy-Sa-N-pregnen-6-one-20-carboxylate, 12 grams of anhydrous lithium iodide, and 100 milliliters of lutidine was heated under reflux for 2 hours. The resulting reaction mixture was poured into ice water, acidified with hydrochloric acid and saturated with sodium chloride. The insoluble reaction product was filtered off by suction, dissolved in methylene chloride and chromatographed twice on silica gel. On recrystallization from acetone/- hexane, there was obtained (2OS),2B,3B- diaeotoxy-5,8-N-pregnen-6-one-20-carboxylic acid, melting point 245247C. There was also recovered methyl (20R),2B,3B-diacetoxy-5B-A pregnen-6-one-20-carboxylic acid, melting point 205.5208C. (from acetone/hexane).

A mixture of 1.9 grams of the (2OS),20-carboxylic acid, 38 milliliters of absolute tetrahydrofuran, and grams of carbonyldiimidazole was heated for minutes under reflux. The resulting reaction solution was poured into ice water, acidified with hydrochloric acid, and saturated with sodium chloride. The insoluble imidazolide was separated and dried. A solution of a 2-gram portion of the imidazolide in 40 milliliters of tetrahydrofuran was treated with 2 grams of lithium tri- (tert.-butoxy)aluminum hydride and then stirred at room temperature for 1 hour. The resulting mixture was then stirred into ice water, acidified with hydrachloric acid and, after buffering with sodium ethylate, extracted with methylene chloride. After distillation of the solvent, chromatographing on silica gel, and crystallization from acetone/hexane, there was obtained (2- 0S),2B,3B-diacetoxy-2O-formyl-5B-A -pregnen-6-one, melting point 200-202C. To an ethyl magnesium bromide solution (produced from 488 milligrams of magnesium and 1.68 milliliters of ethyl bromide in milliliters of ether), there was added 3.86 milliliters of 2-methyl-2-tetrahydropyranyloxy-S-butyne in 20 milliliters of tetrahydrofuran dropwise. After stirring for minutes, the Grignard solution was added to an ice-cooled solution of 820 milligrams of the 20-formyl compound produced as described above in 20 milliliters of tetrahydrofuran and then stirred for 5 minutes. The reaction mixture was treated with saturated ammonium chloride solution and the reaction product was taken up in ether, washed with saturated salt solution, dried and evaporated. After chromatographing on silica gel, there was obtained (22R),2B,3B-diacetoxy-22- hydroxy-25-tetrahydropyranyloxy-S,B-A -cholesten-23- yn-6-one, melting point l75l 78C. (from hexane/ether). The (22S)-isomer (melting point lf72l73C.) was also obtained.

To a solution of 227 milligrams of this product in 10 milliliters of methanol, there was added 60 milliliters of platinum dioxide and the resulting mixture was hydrogenated until hydrogen uptake ceased. After filtration of the catalyst and evaporation of the solvent under vacuum, the residue was crystallized from acetone/hexane to yield (22R),2B,313,22-tri-hydroxy-25- tetrahydropyranyloxy-5fi-N-cholesten-23-yn-6-one, melting point l47l50C.

A solution of 100 milligrams of the thus-produced triol in 2 milliliters of dioxane was treated with 100 milligrams of selenium dioxide and heated for 1 hour at 90C. The resulting reaction mixture was subjected to preparative thin layer chromatography and after crystallization from tetrahydrofuran/petane, there was obtained (22R ),2]3,3B, l4a,22,25pentahydroxy-5B-A cholesten-G-one (ecdyson), melting point 232233C.

Employing the (22S )-isomer isolated after the Grignard reaction, there was produced in a similar manner (22S),2B,3B, l 4a,22,25 -pentahydroxy-5 13-N- cholesten-6-one (isoecdyson), melting point 227-230C. (from acetone).

EXAMPLE V From 3,3-Ethylenedioxy-20-l-lydroxymethyl-N Pregnen 6-one, followed by acetylation to 3B-acetoxy-20- acetoxymethyl-Za-bromo-S -pregnan-6-one (melting point 208209C. and then reacted with silver acetate to produce 2B,3B-diacetoxy-20-acetoxymethylpregnan-6-one as a mixture of the Sa-H- and 53-H- isomers.

Employing procedures similar to those described in Example lVC(Z), the isomeric mixture was brominated methanol was heated at boiling for 30 minutes. The reaction mixture was then processed in a manner similar to the procedure described in Example lC to obtain 2- 3,38, l 4a-trihydroxy-ZO-hydroxymethyl-5a-N- pregnen-6-one, melting point 255-257C. (from tetrahydrofuran-ethyl acetate).

A solution of 200 milligrams of 23,313,140:- trihydroxy-2O-hydroxymethyl-5B-A -pregnen-6-one in 50 milliliters of acetone was treated with 0.2 milliliter of boron trifluoride etherate and processed as described in Example IID. There was obtained 2,8,36- isopropylidenedioxy-l4a-hydroxy-ZO-hydroxymethyl- 5 B-N-pregnen-6-one, melting point 24024lC. (from acetone/hexane) EXAMPLE VI From 3a-l-lydroxy-20,20-Ethylenedioxypregnan-6-one 3a-l-lydroxy-ZO.ZO-ethylenedioxypregnan-6-one was oxidized in known manner to 20,20-ethylenedioxypregnane-3,6-dione. Employing techniques described in Example lVC, the 3,6-dione was brominated to form 2abromo-20.20-ethylenedioxypregnane-3,6-dione, the Za-bromo-compound was reduced with lithium tri(- tert.-butoxy)aluminum hydride to form 2a-bromo-3B- hydroxy-20,20-ethylenedioxypregnan-6-one, the alcohol was converted to the corresponding BB-acetate, and the 2a-bromo-3B-acetoxy-20,20-ethylenedioxy- 5a-pregnan-6-one was reacted with silver acetate to produce 2B,3B-diacetoxy-20,20-ethylenedioxypregnan-6-one as a mixture of the 5ot-H- and SB-H- isomers.

Employing procedures similar to those described in Example IVC, the isomeric mixture was brominated to form 2B,3,8-diacetoxy-7a-bromo-20,20-ethylenedioxy- 5a-pregnan-6-one, followed by dehydrobromination to 2,8,3B-diacetoxy-20,20-ethylenedioxy-5a-N-pregnem 6-one Acidic ketal cleavage in known manner lead to 28,3- B-diacetoxy-Sa-N-pregnene-6,20-dione. This dione was then reacted with 2-methyl-2- tetrahydropyranyloxy-S-bromopentane, employing the known Wittig-reaction techniques, to produce 23,313- diacetoxy-ZS-tetrahydropyranyloxy-5a-A cholestadien-6-one. After selective epoxidation of the N -double bond, hydrolysis of the epoxide to the 20,22-diol and l4a-hydroxylation with selenium dioxide, there was obtained 2B,3,B-diacetoxy-l4a,20,22,25- tetrahydroxy-5a-A -chlesten-6-one.

A solution of 500 milligrams of 2B,3B-diacetoxy- 1 401,20 ,22 ,25-tetrahydroxy-N-cholesten-6-one and 250 milligrams of potassium carbonate in 100 milliliters of methanol was heated at boiling for 50 minutes. The reaction mixture was then neutralized with acetic acid and evaporated to dryness in vacuo. Isolation and purification of the reaction product was accomplished by preparative layer chromatography on silica gel using chloroform-methanol. There was obtained 2833,1401,- 20,22,25-hexahydroxy-SB-N-cholesten-6-one, melting point 237.5-239.5C.

We claim:

1. A compound of the formula:

2. A compound of the formula:

. OH: OH

3. A compound of the formula:

CH-CH-A-AiE-Ro wherein Ra is a hydrogen, hydroxy or a radical derived from an aliphatic carboxylic acid of from two to l 1 carbon atoms by removal of the hydrogen of a carboxyl group: R is hydroxy, a radical derived from an aliphatic carboxylic acid of from two to l 1 carbon atoms by removal of the hydrogen of a carboxyl group; A is Cl-l Cl-l or C C; R is hydrogen or hydroxy, Y is hydrogen or a radical derived from an aliphatic carboxylic acid of from two to l 1 carbon atoms by removal of the hydroxy moiety of a carboxyl group; R is hydroxy or a radical derived from an aliphatic carboxylic acid of from two to 1 1 carbon atoms of the hydrogen of the carboxyl group or tetrahydropyranyloxy.

4. A compound of the formula:

\Rv I OH wherein R and R independently are hydroxy or a radical derived from an aliphatic carboxylic acid of from 2 to 11 carbon atoms by removal of the hydrogen of a carboxyl group or R and R when taken together, when R is in the beta-position, form lower alkylenedioxy; R is hydrogen or hydroxy; R when R is hydrogen is:

n CH: -oHoH-cH J:H-CH3 or when R is hydroxy, l is wherein R and R independently are hydroxy or a radical derived from an aliphatic carboxylic acid of from two to l 1 carbon atoms by removal of the hydrogen of a carboxyl group; or R and R when taken together, when R is the beta-position form lower alkylenedioxy; R is hydrogen; A is a single or double bond; R is:

R and R are hydrogen, hydroxy, a radical derived from an aliphatic carboxylic acid of from two to I 1 carbon atoms by removal of the hydrogen of the carboxyl group; or tetrahydro-pyranyloxy; and G is -CH-, 2 -CHZ, or C 6. The process for producing a compound of the formula:

wherein Ra is a hydrogen, hydroxy or a radical derived from an aliphatic carboxylic acid of up to ll carbon atoms by removal of the hydrogen of a carboxyl group; R is hydroxy, a radical derived from an aliphatic carboxylic acid of from two to 11 carbon atoms by removal of the hydrogen of a carboxyl group; R is hydrogen or hydroxy; R is hydroxy or a radical derived from an aliphatic carboxylic acid of from two to H, carbon atoms by removal of the hydrogen of the carboxyl group, or tetrahydropyranyloxy; comprising reacting a compound of the formula:

wherein Ra, R R, A and R are as above; with a Grignard reagent of the formula:

R MgX wherein R is CH, -CEC-R.;

R is as above; X is chlorine, bromine or iodine, and the dotted bond can be optionally hydrogenated.

7. A process for producing a compound of the formula:

wherein R, and R independently are hydroxy or a radical derived from an aliphatic carboxylic acid of from 2 to 11 carbon atoms by removal of the hydrogen of a carboxyl group; or R and R when taken together, when R is in the beta-position, form lower alkylenedioxy; R is hydroxy or a radical derived from an aliphatic carboxylic acid of from two to l 1 carbon atoms by removal of the hydrogen of the carboxyl group, and tetrahydropyranyloxy; comprising reacting a compound of the formula:

wherein R and R are as above; with a Grignard reagent of the formula:

CH! R I wherein R and R are as above; with a compound of the formula:

wherein X is chlorine, iodine and bromine; and R is as above,

9. The compound of claim 5 wherein said A is a double bond.

10. The compound of claim 9 wherein R is 4-methyl pent-l-yl.

l 1. The compound of claim 5 wherein R is 4-methyl- 4-tetra-hydropyranyloxy-pent-Z-ynel -y1.

12. The compound of claim 11 wherein R and R are both hydroxy.

13. The compound of claim 4 wherein R is 3, 4- dimethyl pentan-l-yl.

14. The compound of claim 4 wherein R is 4-methylpent-l-yl.

15. The compound of claim 14 wherein R and R are both beta-hydroxy.

16. The compound of claim 14 wherein both R and R are beta-acetoxy.

17. The compound of claim 14 wherein R is acetoxy and R is beta-hydroxy.

18. The compound of claim 4 wherein R is 3 ,4-dimethyl-pentl -ene- 1 -yl.

19. The compound of claim 18 wherein R and R are both beta-acetoxy.

20. The compound of claim 4 wherein R is hydroxy.

21. The compound of claim 20 wherein R is 1,4- dihydroxy-4-methyl-pentl -yl. 

2. A compound of the formula:
 3. A compound of the formula:
 4. A compound of the formula:
 5. A compound of the formula:
 6. The process for producing a compound of the formula:
 7. A process for producing a compound of the formula:
 8. A process for producing a compound of the formula:
 9. The compound of claim 5 wherein said A is a double bond.
 10. The compound of claim 9 wherein R6 is 4-methyl pent-1-yl.
 11. The compound of claim 5 wherein R6 is 4-methyl-4-tetra-hydropyranyloxy-pent-2-yne-1-yl.
 12. The compound of claim 11 wherein R1 and R2 are both hydroxy.
 13. The compound of claim 4 wherein R7 is 3, 4-dimethyl pentan-1-yl.
 14. The compound of claim 4 wherein R7 is 4-methyl-pent-1-yl.
 15. The compound of claim 14 wherein R1 and R2 are both beta-hydroxy.
 16. The compound of claim 14 wherein both R1 and R2 are beta-acetoxy.
 17. The compound of claim 14 wherein R1 is acetoxy and R2 is beta-hydroxy.
 18. The compound of claim 4 wherein R7 is 3,4-dimethyl-pent-1-ene-1-yl.
 19. The compound of claim 18 wherein R1 and R2 are both beta-acetoxy.
 20. The compound of claim 4 wherein R5 is hydroxy.
 21. The compound of claim 20 wherein R7 is 1,4-dihydroxy-4-methyl-pent-1-yl. 